(4S,5R)-3-{[6-azetidin-1-yl-3-(2-methoxy-5-nitrophenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one → (4S,5R)-3-{[3-(5-amino-2-methoxyphenyl)-6-azetidin-1-ylpyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1508510Notes

Reaction equation

HRID 1508510 reaction equation
[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8]([C:33]3[CH:38]=[C:37]([N+:39]([O-])=O)[CH:36]=[CH:35][C:34]=3[O:42][CH3:43])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1>CCO.[Pd]>[NH2:39][C:37]1[CH:36]=[CH:35][C:34]([O:42][CH3:43])=[C:33]([C:8]2[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])=[N:10][C:5]([N:1]3[CH2:4][CH2:3][CH2:2]3)=[CH:6][CH:7]=2)[CH:38]=1

Participants

4

Reactant 1

HCID 86704601(4S,5R)-3-{[6-azetidin-1-yl-3-(2-methoxy-5-nitrophenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 86704602(4S,5R)-3-{[3-(5-amino-2-methoxyphenyl)-6-azetidin-1-ylpyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of (4S,5R)-3-{[6-azetidin-1-yl-3-(2-methoxy-5-nitrophenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (1.26 g, 2.064 mmol) in EtOH (80 mL) was added Pd—C (10%) (0.220 g, 0.206 mmol). The mixture was subjected to hydrogenation by using a Hz balloon for 6.5 h. The mixture was filtered through Celite® and the filtrate was concentrated in vacuo. This was purified by flash chromatography (Biotage Horizon, 40M, Si, ˜30 mL/min, 100% hexanes for 260 mL, gradient to 50% EtOAc in hexanes over 2240 mL) to afford (4S,5R)-3-{[3-(5-amino-2-methoxyphenyl)-6-azetidin-1-ylpyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=580.2. found=581.1 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.86 (s, 1H); 7.75 (s, 2H); 7.32 (d, J=8.3 Hz, 1H); 6.79 (d, J=8.6 Hz, 1H); 6.68 (dd, J=8.6, 2.9 Hz, 1H); 6.54 (d, 2.9 Hz, 1H); 6.27 (d, J=8.3 Hz, 1H); 5.61 (d, J=8.5 Hz, 1H); 4.93-4.30 (m, 1H); 4.18-4.01 (m, 6H); 3.70 (s, 3H); 3.51 (s, br, 2H); 2.46-2.37 (m, 2H); 0.68 (s, br, 3H).

Workup

  1. customfor 6.5 h
  2. filtrationThe mixture was filtered through Celite®
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThis was purified by flash chromatography (Biotage Horizon, 40M, Si, ˜30 mL/min, 100% hexanes for 260 mL, gradient to 50% EtOAc in hexanes over 2240 mL)

Sources & evidence

ORD record
ord-99da0c9c54144007aa17bbf65956f997
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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